Nanoscale drug delivery systems and biomedical sensors are witnessing huge research interests. Polymeric nanoparticles, nanofibers, liposomes, and nano-emulsion are regarded as novel sensors and drug delivery systems including the various types of wound dressings formulated by micro/nanofibers, hydrogels, hydrocolloids, films, foams, and sponges. Consequently, the electro-spun nanofibrous mats received the most attention since the drugs and nanoparticles embedded nanofibers have been recognized as the potential candidates for sensors and wound dressing applications. These composite materials have superior surface area-to-volume ratio, high nano-porosity, distinct skin extracellular matrix structure, and ease of electro-spinning, which also supports a prolonged drug release. In this study the main advantages of the nano-fibrillary network and the active substances that can be incorporated in fabricating the composite nanofibers as sensors and wound dressing materials are discussed. The promising “Pluronic F68” and polyvinyl alcohol (PVA), materials are used including nanoparticles (NPs) of titanium dioxide (TiO2), silver, and cobalt. The difficulties that arise by converting the Pluronic into nanofibers via electrospinning due to its low melting point and beads formation and the blending of this material with polyvinyl alcohol (PVA) are discussed. The electro-spinability of the pure Pluronic, PVA and their blends are evaluated. The microstructures and morphologies of the fabricated composite nanofibers and structures are characterized using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential thermal analysis (DSC), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). The fabricated blended nanofibers were found to be compact and entangled having a diameter from 50 nm to 80 nm and length ranging from 1 to 3 μm. Meanwhile, the pure Pluronic produced nano-beads with an average size of 40 nm. These nanocomposites can be used in biomedical applications such as biosensors by embedding nanoparticles of TiO2, silver, and cobalt and for antibacterial treatment in woundcare dressings.